Biomarker Testing in NSCLC to Expand in Near Future

The process of testing for EGFR/ALK/ROS1 as well as PD-L1 to identify molecular targets in patients with non–small cell lung cancer (NSCLC) is expected to transform over the next couple of years, as novel, next-generation biomarkers are currently being explored.

“It is such an exciting time in lung cancer. We historically only had chemotherapy to offer to our patients, and now we have 3 pillars: chemotherapy, targeted therapies, and now immunotherapy,” said Matthew Gubens, MD. “Now, trying to choose the right patient, for the right therapy, at the right time is becoming increasingly important. Therefore, we have to be savvy about how we get tissue and how we use tissue.”

Gubens, an assistant professor of thoracic oncology at the University of California San Francisco, lectured on biomarker testing in NSCLC during the 2017 OncLive® State of the Science Summit on Advanced Non–Small Cell Lung Cancer. In an interview, he shed more light on how far the field has come with molecular testing, the challenges still ahead, and what novel assays could be on the horizon.

Gubens: Who do we need to look for targets in so we can give the right targeted therapy? Of course, that starts with the economical EGFR/ALK/ROS1 test and what the FDA tells us we can give, but also looking at some of the emerging targets, such as HER2, BRAF, and MET, where we have enough data in phase II trials to at least get us interested, if not putting a patient on trial and offering off-label drugs.

Some of those targets are in patients whom we really haven’t historically thought of for targeted therapy. It is just going to become even more important to offer this kind of testing across the board to all nonsquamous and, eventually and hopefully, squamous patients.

We are also now talking about PD-L1 testing with the advent of immunotherapy in the first-line setting. It is going to be so important to choose the right PD-L1 tests to figure out who we can offer the therapy to in the first-line setting, and who we have to hold off and do other treatments for first.

Aside from getting the tissue and using it, what other modalities can we use? The whole field of liquid biopsies is coming on fast and furious and it’s such an exciting opportunity to get noninvasive testing in a way that might sample the whole extent of metastatic tumor, but also fraught because we need to make sure we use it in a smart way and not displace our gold standard. How we use tissue and liquid together in a smart, complimentary way is the challenge going forward.

Finally, how do we rebiopsy? When is it appropriate and important to go back and get more tissue or blood to choose a next-line therapy? EGFR is pointing the way with the third-generation tyrosine kinase inhibitor (TKI) osimertinib (Tagrisso). It is also just setting a new paradigm where I hope that, 1 or 2 years from now, we are going to talk about rebiopsying ALK or ROS1. We need to understand how tumors evolve and be smart about offering precision medicine, not just as a step 1, but steps 1, 2, 3, and 4.

Let’s say you get a patient with newly diagnosed NSCLC. Do you test them for PD-L1 expression and EGFR/ALK/ROS1 simultaneously, or does 1 molecular test come first?

This is a huge challenge right? Partly, you are dealing with a situation where, sometimes, there’s not that much tissue to go around, especially in lung cancer. Is that enough to answer all of the questions we just posed?

That is part of the challenge with working with our multidisciplinary teams to, first of all, make sure we get enough tissue to answer our questions. Secondly, to make sure that the turnaround time is one that we can actually treat the patient clinically.

Your question is spot-on. A lot of us [are] trying to figure out whether you [should] check for a few things initially; that can be easy on the tissue but then adds up costs. We are really moving to a place where it’s nice to be able to do multiplex testing from the beginning. In the end, it’s probably cost effective because you can do a lot of tests on a little tissue.

The downside, of course, is that sometimes that can take a while to come back. If you don’t have 3 to 4 weeks to get a decision, how can we use other tools to get that decision quicker? Some of us are using short-term targeted genomics for some targets such as EGFR, we might use fluorescence in situ hybridization, which comes back quick for ALK and ROS1, while PD-L1 is an immunohistochemistry test that should come back within 1 week.